Targeting Liver Metastases to Potentiate Immunotherapy In MS-stable colorectal cancer- A Scoping Review of Literature

Abstract While Immunotherapy has revolutionized the treatment of several cancers such as lung cancer, melanoma, and other cancers, most colorectal cancer patients remain resistant. This resistance to immunotherapy may partially stem from the fact that colorectal cancer very commonly metastasizes to the liver. The liver is known to play an immunotolerant role in in other contexts such as organ transplantation, viral disease, and autoimmune disease. Recent studies reveal the mechanisms in which liver metastases restrict the efficacy of immunotherapy. This effect was shown to be reversable in colorectal cancer mice models, when colorectal liver metastases were irradiated. It is possible that targeting liver metastases with locoregional therapies such as ablation, resection or irradiation may reverse the immunosuppressive effect of liver microenvironment and potentiate immunotherapy systemically. During the past decade, several clinical trials are trying to extrapolate the results achieved in animal model to clinical trials by combining immunotherapy with locoregional therapy. In this scoping review, the current clinical and translational literature was surveyed, to determine whether there is evidence to support the validity of this concept in human patients. If indeed immunotherapy can be potentiated for MS- Stable colorectal cancer utilizing locoregional interventions, a wide array of innovative protocols can be utilized to help cancer patients who have no other available treatment options and thus revolutionize the treatment of cancer patients with liver metastases.